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Systematic Review

Do Exercise, Physical Activity, Dietetic, or CombinedInterventions Improve Body Weight in New Kidney TransplantRecipients? A Narrative Systematic Review and Meta-Analysis

Ellen M. Castle 1,2,3,* , Emily McBride 4, James Greenwood 5, Kate Bramham 2,6, Joseph Chilcot 7

and Sharlene A. Greenwood 1,2,3

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Citation: Castle, E.M.; McBride, E.;

Greenwood, J.; Bramham, K.; Chilcot,

J.; Greenwood, S.A. Do Exercise,

Physical Activity, Dietetic, or

Combined Interventions Improve

Body Weight in New Kidney

Transplant Recipients? A Narrative

Systematic Review and

Meta-Analysis. Kidney Dial. 2021, 1,

100–120. https://doi.org/10.3390/

kidneydial1020014

Academic Editor: Giorgina

Barbara Piccoli

Received: 9 August 2021

Accepted: 14 September 2021

Published: 2 October 2021

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1 Therapies Department, King’s College Hospital NHS Trust, London SE5 9RS, UK;[email protected]

2 King’s Kidney Care, King’s College Hospital, London SE5 9RS, UK; [email protected] Renal Sciences, King’s College London, London SE5 9RS, UK4 Department of Behavioural Science and Health, Institute of Epidemiology and Health Care, University

College London, London WC1E 6BT, UK; [email protected] Victor Horsley Department of Neurosurgery, University College London Hospital, London WC1N 3BG, UK;

[email protected] Department of Women and Children’s Health, Faculty of Life Sciences and Medicine, King’s College London,

London SE5 9RS, UK7 Department of Health Psychology, King’s College London, London SE1 9RT, UK; [email protected]* Correspondence: [email protected]; Tel.: +44-020-8194-7470

Abstract: Weight gain within the first year of kidney transplantation is associated with adverseoutcomes. This narrative systematic review and meta-analysis examines the effect of exercise,physical activity, dietary, and/or combined interventions on body weight and body mass index (BMI)within the first year of kidney transplantation. Seven databases were searched from January 1985 toApril 2021 (Prospero ID: CRD42019140865), using a ‘Population, Intervention, Controls, Outcome’(PICO) framework. The risk-of-bias was assessed by two reviewers. A random-effects meta-analysiswas conducted on randomized controlled trials (RCTs) that included post-intervention body weightor BMI values. Of the 1197 articles screened, sixteen met the search criteria. Ten were RCTs, andsix were quasi-experimental studies, including a total of 1821 new kidney transplant recipients.The sample sizes ranged from 8 to 452. Interventions (duration and type) were variable. Random-effects meta-analysis revealed no significant difference in post-intervention body weight (−2.5 kg,95% CI −5.22 to 0.22) or BMI (−0.4 kg/m2, 95% CI −1.33 to 0.54). Despite methodological variance,statistical heterogeneity was not significant. Sensitivity analysis suggests combined interventionswarrant further investigation. Five RCTs were classified as ‘high-risk’, one as ‘some-concerns’, andfour as ‘low-risk’ for bias. We did not find evidence that dietary, exercise, or combined interventionsled to significant changes in body weight or BMI post kidney transplantation. The number andquality of intervention studies are low. Higher quality RCTs are needed to evaluate the immediate andlonger-term effects of combined interventions on body weight in new kidney transplant recipients.

Keywords: kidney transplant; weight gain; body weight; systematic review; physical activity;meta-analysis

1. Introduction

Weight gain within the first year of solid organ (kidney, liver, heart, and lung)transplantation has been associated with adverse clinical events and poor transplantoutcomes [1,2]. Whilst weight gain presents as a clinical issue for all solid organ transplant(SOT) recipients, the experiences of weight gain vary across the SOT groups. Liver trans-plant recipients tend to have a reduction in body weight in the first six months associatedwith the removal of ascites, followed by a period of weight gain [3]. In contrast, kidney,

Kidney Dial. 2021, 1, 100–120. https://doi.org/10.3390/kidneydial1020014 https://www.mdpi.com/journal/kidneydial

Kidney Dial. 2021, 1 101

heart, and lung transplant recipients demonstrate rapid weight gain in the acute-postoperative period [3].

Increased body weight and body mass index (BMI) is associated with poor transplantoutcomes. A retrospective analysis of 25,539 adult kidney transplant recipients (KTRs) inthe United Kingdom (UK) reported a BMI of greater than 25 kg/m2 was an independentrisk factor for both delayed graft function and primary graft non-function [4]. In addition,underweight and obese KTRs were reported to have poorer graft survival [4].

Weight gain within the first year of receiving a kidney is a critical health issue [5]. KTRswho gain more than 15% of their body weight within the first year of transplant surgeryare at an increased risk of death with a functioning kidney [6]. The factors underlyingpost kidney transplant weight gain include reduced physical function [7] and physicalactivity (PA) [8], increased appetite [9], steroid medication use [10], and the lifting of dietaryrestrictions [11].

Results from a recent UK survey of all transplant centres revealed clinicians believedthat kidney transplant outcomes were adversely affected by obesity. [4] Despite this recog-nised clinical need, dedicated pathways to address weight management for KTRs weresparse with variable access [4].

Previous literature reviews [12,13], systematic reviews [14,15], and meta-analyses [16,17]that examine the effects of exercise [12,15–17] or PA interventions [13,14] for KTRs haveshown a favourable effect on cardiorespiratory fitness and exercise tolerance [13,15–17],muscle strength and function [16,17], health-related quality of life [13,15,16], maximumheart rate [15], and arterial stiffness [17]. Exercise studies have failed to show significanteffects on body weight or composition [15]. However, combined interventions that includedany combination of either exercise, physical activity, and/or dietary interventions wereexcluded in these reviews.

A Cochrane review of dietary interventions for adults with end-stage kidney dis-ease (including KTRs), concluded clinical dietary care recommendations could not bemade for KTRs due to insufficient evidence [18]. This Cochrane review excluded dietaryinterventions that incorporated strategies to implement lifestyle behaviour-change.

Currently, there are no systematic reviews and meta-analyses that consider the impactof either exercise, physical activity, dietary, or combined interventions on body weightand BMI in KTRs within the first year of receiving a kidney transplant. The researchquestion for this systematic review was ‘do exercise, physical activity, dietetic, or combinedinterventions improve body weight in new kidney transplant recipients?’ The aim of thisnarrative systematic review and meta-analysis was to provide a synthesis and pooled effectof post-transplant interventions on body weight and BMI within the first year of kidneytransplantation and suggest recommendations for future research.

2. Materials and Methods2.1. Search Protocol and Registration

A pre-specified protocol was published on the 9th September 2019 (www.crd.york.ac.uk/PROSPERO, accessed on 9 September 2019, id: CRD42019140865). This narrativesystematic review and meta-analysis was undertaken as per the Preferred Reporting Itemsfor Systematic Reviews and Meta-Analyses (PRISMA) guidance [19], (Supplementary Ma-terial, Table S1). Eligibility criteria were based on the ‘Population, Intervention, Controls,Outcome’ (PICO) framework [20,21], and are summarised in Table 1. The population ofinterest was new KTRs within the first year of kidney transplantation. Post-transplantinterventions consisted of either exercise, physical activity, dietary interventions, or a com-bination thereof. PA was defined as any habitual or planned activity of the body such asoccupational, transportation, domestic, and social [22]. In contrast, exercise interventionswere defined as any planned, structured, prescriptive activity designed to improve a spe-cific aspect of physical fitness [22,23]. Dietary interventions included dietary modifications,advice, nutritional counselling, and education regarding food-based interventions [18].Combined interventions refer to any combination of exercise, PA, and/or dietary interven-

Kidney Dial. 2021, 1 102

tions. They may also include behaviour change techniques (BCTs) designed to address PAand/or healthy eating behaviour(s) [24].

Table 1. Eligibility criteria based on the PICO framework.

PICO(s) Inclusion Exclusion Reasons for Exclusion

Population KTRs within the first 12 months oftransplantation

>12 months post-transplant<18 years of age

Mixed samples (e.g., dialysis andtransplant patients)

WG occurs within first yearDifferent populations (adults vs.

paediatric)Difficult to isolate effects to just

KTR in mixed sample unlessinformation provided by authors

Intervention

Complex interventions involvingeither exercise, activity, nutrition,

diet, behaviour-change, orcombined interventions designed

to prevent WG occurring

Treatments includingpharmacological intervention

Difficult to isolate effects of theother components of the treatment

Comparator Usual care or standard care or nointervention No comparator available Difficult to determine the

treatment effect(s)

Outcomes-Primary outcomeWG from baseline to short term (3

months) baseline to long term(6–12 months)

No reported BW or BMI atbaseline or follow-up (3–12

months)

Unable to determine change inBW or BMI

Study Types RCTs, non-RCTs(quasi-experimental)

Exclude literature reviewsExclude trials with no control

groupOutside scope of this review

Language English Limited resources for this project

Year Published after 1985 Changes to standards of care

Note. KTR indicates kidney transplant recipient, BW = body weight, WG = weight gain, CKD = chronic kidney disease, RCTs = randomisedcontrolled trials, Non-RCTs = nonrandomised controlled trials.

As weight gain is of clinical concern, particularly within the first year of receiving akidney transplant, interventions were included if they were offered within the first year ofreceiving the kidney transplant. Table S2 demonstrates the search strategy. RandomisedControlled Trials (RCTs) and quasi-experimental studies (non-RCTs) with a comparatorgroup were included. The primary outcome of interest was post-intervention measuresof body weight or BMI. Long-term follow-up of body weight and BMI were included ifavailable. Secondary outcomes included body composition, physical function, PA levels,self-efficacy toward PA, and mood. This systematic review will focus on body weight andBMI from the RCTs. Secondary outcomes and non-RCTs will be presented briefly.

2.2. Study Identification

MEDLINE, Embase, Psychinfo, CINAHL, SCOPUS, The Cochrane Library, and Webof Science were searched from the 1st January 1985 to the 6th April 2021. Grey literaturewas searched using OpenGrey. A combination of free text searching, subject headings, andBoolean operators were used. This search strategy was piloted and refined by authors andsubject matter experts, with assistance from librarians. Search terms were adapted to eachdatabase. The final search was conducted by two authors (E.M.C. and J.G.). Conferenceabstracts were searched for full text publications, and reference lists were hand-searched.

2.3. Study Selection, Data Extraction, and Risk-of-Bias

All stages of the review were recorded on an Excel spreadsheet and Endnote software.Duplicate citations were removed. The remaining citations were assessed against thepre-defined eligibility criteria. Title and abstracts that did not meet the search criteria wereexcluded. The remaining full text articles were assessed for eligibility (E.M.C. and J.G.).Table S3 depicts the screening form.

Data were extracted from the full text publications and tabulated, based on the ‘char-acteristics included in studies table’ in the Cochrane Handbook for Systematic Reviews ofInterventions [25]. In addition, ten percent of titles and abstracts, and ten percent of the full

Kidney Dial. 2021, 1 103

text citations were selected using a random number generator and assessed for eligibilityby two subject matter experts (J.C. and S.G.). When missing data were encountered, thecorresponding author was contacted via email. If no response was received, this wasrepeated with secondary and senior manuscript authors.

Two reviewers (E.M.C. and E.Mc.) independently assessed the final full text publi-cations using version two of the Cochrane risk-of-bias tool for randomized studies [26]and the risk-of-bias in non-randomized studies of interventions tool [27]. If disagreementsoccurred, both reviewers would discuss until consensus was achieved. Where consensuscould not be achieved, a third reviewer (S.G.) would resolve disagreements.

2.4. Statistical Analysis

The Cochrane handbook [28] was utilised to calculate standard deviations (SD) basedon the available data reported. RCTs that reported post-intervention body weight (n = 8)and post-intervention BMI (n = 8) for an intervention group (either diet, PA, exercise, orcombined interventions) and a comparator group (usual care or no intervention) wereincluded in the meta-analysis. This allowed for calculation of an estimate of pooled effectof the interventions on body weight and BMI, with associated confidence intervals todemonstrate precision. Meta-analysis was not completed for secondary outcomes in thissystematic review due to the variation in measurement scales.

Post-intervention values (body weight and BMI) were used rather than change scoresfor the meta-analysis. There was inadequate data from the studies to calculate confidenceintervals for change-scores in body weight and BMI values in all RCTs. Secondly, meta-analyses with post-intervention values have been shown to have more a conservativeestimate of effect than change scores [29]. For the studies with more than one treatmentarm, guidance was used to combine means and SDs to form an intervention group meanwith SD [30,31].

Meta-analyses were conducted using RevMan software [32]. The inverse model forcontinuous data and the Der Simonian and Laird [33] random-effects model were usedto produce a pooled estimate of effect. A random-effects model was selected due to theanticipated heterogeneity caused by clinical and methodological differences between theRCTs [34].

Forrest plots, with chi squared and I2 statistics were used to assess heterogeneitybefore proceeding with the meta-analysis as per the Cochrane handbook [35]. Due to thesmall number of RCTs included in each meta-analysis, and the methodological variationin trial designs, sub-group analysis was not completed. Heterogeneity and publicationbias were explored using funnel plots [34]. A post hoc exploratory sensitivity analysiswas performed to examine the potential influence of different intervention types on bodyweight and BMI values.

3. Results3.1. Search Results and Study Characteristics

After the removal of duplicates, 1198 citations were reviewed for eligibility. Thissystematic review revealed eighteen publications, from sixteen studies that met the searchinclusion criteria. Four publications [36–39] were from two studies. O’Connor et al. [39]reported a long-term follow-up of the same participants of the original study by Greenwoodet al. [38]. Therefore, these two studies [38,39] were considered as one intervention for thepurpose of this systematic review and meta-analysis. Painter et al. [36,37] were publicationsfrom the same trial, and were also considered as one intervention. Figure 1 summarises thestudy selection process utilising a PRISMA diagram [40].

Kidney Dial. 2021, 1 104

Kidney Dial. 2021, 1, 5

produce a pooled estimate of effect. A random-effects model was selected due to the an-ticipated heterogeneity caused by clinical and methodological differences between the RCTs [34].

Forrest plots, with chi squared and I2 statistics were used to assess heterogeneity be-fore proceeding with the meta-analysis as per the Cochrane handbook [35]. Due to the small number of RCTs included in each meta-analysis, and the methodological variation in trial designs, sub-group analysis was not completed. Heterogeneity and publication bias were explored using funnel plots [34]. A post hoc exploratory sensitivity analysis was performed to examine the potential influence of different intervention types on body weight and BMI values.

3. Results 3.1. Search Results and Study Characteristics

After the removal of duplicates, 1198 citations were reviewed for eligibility. This sys-tematic review revealed eighteen publications, from sixteen studies that met the search inclusion criteria. Four publications [36–39] were from two studies. O’Connor et al. [39] reported a long-term follow-up of the same participants of the original study by Green-wood et al. [38]. Therefore, these two studies [38,39] were considered as one intervention for the purpose of this systematic review and meta-analysis. Painter et al. [36,37] were publications from the same trial, and were also considered as one intervention. Figure 1 summarises the study selection process utilising a PRISMA diagram [40].

Figure 1. Flow chart of study selection process with reasons for exclusion. Where n = number of studies, P = population of interest, S = study design, O = outcome of interest, Randomised Con-trolled trials (RCTs) only included in this analysis. Figure adapted from: Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffman TC, Mulrow CD, et al. The PRIMSA 2020 statement: an updated

Figure 1. Flow chart of study selection process with reasons for exclusion. Where n = number ofstudies, P = population of interest, S = study design, O = outcome of interest, Randomised Controlledtrials (RCTs) only included in this analysis. Figure adapted from: Page MJ, McKenzie JE, Bossuyt PM,Boutron I, Hoffman TC, Mulrow CD, et al. The PRIMSA 2020 statement: an updated guideline forreporting systematic reviews. BMJ 2021; 372:n71, doi:10.1136/bmj.n71. For more information visithttp://www.prisma-statement.org/.

From the sixteen final studies, ten were RCTs, and six were non-RCTs (quasi-experimentalstudies) with a total of 1821 KTR participants within the first year of kidney transplantation.The individual study sample sizes ranged from eight [41] to 452 participants [42]. Two ofthe four studies include other transplant populations [43,44]; however, one author was ableto provide data for the KTR sub-group on request [43].

There was variation across the sample characteristics that could limit the generalisabil-ity (see Tables 2 and 3). Some trials excluded KTRs with diagnosed diabetes [45–48], anotherstudy included hyperlipidaemic KTRs [45], and two studies included only overweight orobese KTRs [42,49]. See Table S4 for detailed study sample characteristics.

Six studies reported body weight only [39,41,44,47,48,50], four reported BMI [43,45,49,51],and six reported both body weight and BMI [36,42,43,46,52,53] post-intervention. Sevenout of the sixteen studies recorded body weight or BMI at an interim time point of three tosix months, and at a one-year follow-up [36,39,45,49,50,52,54]. Only three trials [39,50,52]included a long-term follow-up of body weight or BMI after the intervention cessation,making it difficult to determine longer-term intervention effects. Table 2 summarizesthe study characteristics of the included RCT studies (n = 10).Table S5 (SupplementaryMaterial) summarizes the non-RCTs (n = 6).

Kidney Dial. 2021, 1 105

Table 2. Summary of characteristics of included RCTs (n = 10).

First Author, Year (Countryof Origin)

StudyDuration (Months) Sample Groups Outcomes (Primary and

Secondary)Results (for Primary and

Secondary Outcomes) Comments

Lawrence et al. [45](UK) 12 n = 38, KTRs with

hyperlipidaemia

IG:Dietitian only for 12 months

CG:Usual care, no dietary

intervention

Primary:Dietary intake (24-h recallassessed for total energy

intake, fibre intake, protein,carbohydrate, fat and

distribution of fat intake)and

fasting lipidsSecondary:BW, BMI,

medications, Renal function

Primary:No significant differencebetween groups in total

cholesterol, HDLcholesterol, or plasma

triglyceride levelsLDL cholesterol was

significantly lower in the IGat 1 month after Tx

Significant improvement inpolyunsaturated-to-

unsaturated fat ratio in theIG

Change in dietary intake notassociated with changes in

serum lipid levelsFibre intake significantly

higher at 3 months in the IGSecondary:

No difference in BMI,medication, or kidney

function between groups atany time

Both groups reducedaverage consumption of

cigarettes and alcohol

AEs not reportedLimited reporting ofblinding, allocation,

analysis plan, treatment,protocol deviations, and

statistical plan

Painter et al. [36](USA) 12 n = 167

IG:12-months ET, home based

ATCG:

no ET

Primary:Not statedSecondary:

VO2 peak, Muscle strength,BC (DEXA), QoL (SF-36), PAreporting (active or inactive)

Primary/Secondary:No difference in BW, BMI,

or BC, all participantsincreased BW, BMI, FM,

LTM, % FMIG had greater gains in VO2

peak and muscle strengthIG had higher % classified

as active at follow-upNo difference in QoL

AEs not reportedHigh dropout rate

42% did not completeassessment at all three

timepointsPainter 2003 duplicate paper

from this study

Tzvetanov et al. [49](USA) 12 n = 17, Obese KTRs

IG:12-month combined Rx

(lifestyle, exercise,behaviour, and nutrition

guidance)CG:

Nutritional guidance only

Primary:Not stated? feasibility

Secondary:Physical (weightliftingcapacity) and vascular

function (PWV and CiMT),BC, QoL (SF-36), kidney

function, blood lipidmarkers, and adherence

Primary/Secondary:No significant difference in

BMI at 12 monthsGreater adherence to

follow-up in IG (100%) vs.CG (25%)

Improved weightlifting andPWV (IG only)

significant difference inCiMT (IG only)

Improvement in QoL (p =0.008) and employment rate

(p = 0.02) in IG vs. CGNo significant differencesbetween groups in kidney

function or lipids

AEs not reportedSmall sample

t-tests used, not ITTHigh dropouts in CG vs. IG

Missing data (BC, PWV,CiMT) in CG

Karelis et al. [46](Canada) ≈4 n = 24, non-diabetic KTRs,

excluded smoking history

IG:Exercise only for 16 weeks

(RT)CG:Instructed not to perform

any structured exercise

Primary:Feasibility outcomes(adherence, injuries,

drop-outs)Secondary:

BC (DEXA), OGTT, Lipidprofile, BP, QoL,

Anthropometrics,Muscle strength (leg press),

VO2 peak

Primary:47% consent rate

80% compliance IG17% dropout IG

Secondary:No difference in BW or BMI,BC, VO2 peak, lipids, OGTT

or QoLBoth groups increased FM

(BC)IG associated with increase

in muscle strength (p =0.003)

No AEs or injuries reportedShort study duration (16

weeks)Small sample size

O’Connor et al. [39](UK) 12 n = 47 of the original 60

ExeRT cohort [38]

IG1:Supervised AT for 12 weeks

IG2:Supervised RT for 12weeks

CG:No ET for 12 weeks

Primary:PWV and VO2 peak

Secondary:Anthropometrics, BP

Primary:Significant difference in

PWV in IG2 (RT) vs. CG (p =0.03)

Favourable difference inVO2 peak IG1 (AT) vs. CG

(p = 0.02)Secondary:

No differencebetween-groups in BW or

BPBMI not reported

No difference in BMIreported in original study

manuscript [38]

No AEsLong-term follow-up datafrom the ExeRT cohort [38]

DropoutsANCOVA used

Kidney Dial. 2021, 1 106

Table 2. Cont.

First Author, Year (Countryof Origin)

StudyDuration (Months) Sample Groups Outcomes (Primary and

Secondary)Results (for Primary and

Secondary Outcomes) Comments

Henggeler et al. [54](NZ) 12 n = 37 KTRs with a BMI of >

18.5 and <40 kg/m2

IG:12-month combined Rx

including standard care +dietitian appointments (12

sessions in total) andexercise sessions

CG:Standard care (4 sessions in

12 months) with renaldietitian

Primary:BW at 6 months adjusted for

baseline weight, obesity,and genderSecondary:

Change in Anthropometricsand BC (DEXA), resting

energy expenditure,physical function (grip,

25-feet gait speed, STS), PA(NZ PA questionnaire),

serum biochem, QoL (SF-36)

Primary:No significant difference inBW or BC between groups

at 6 monthsSecondary:

No between-groupdifference in BC or energy

expenditureBoth groups increased total

body fat and % body fatNo significant difference in

biochemistryWhole sample HbA1c andfasting glucose increased,

cholesterol decreasedWhole sample improvedphysical function, body

protein, and QoL

No AEsCG greater than clinical

practice in the UKMay require formal ET/PAto elicit training response

ANCOVA used

Kuningas et al. 2019 [48](UK) 6 n = 130 nondiabetic KTRs

IG:6-month exercise and

nutrition education +BCTsCG:

Passive education (booklet)on healthy eating, exercise,

and risks of PTDM

Primary:6-month change in insulinsensitivity, secretion, anddisposition index (OGTT)

Secondary:PA (GPPAQ), Physicalfunction (DASI), QoL

(EQ-5D), Beck depressioninventory, situational

motivational score, safetyissues, BW, BC (skinfolds

and bioimpedance)

Primary:No between-group

difference in 6-monthglucose metabolism

Secondary:Significant between-groupdifference in BW favouring

IG vs. UC (p = 0.02)Significant between-groupdifference in FM IG vs. CG

(p = 0.03)Clinically significant

reduction in PTDM, halvedin IG vs. CG

No between-groupdifference in anyquestionnaires

No safety concernsDropout out rate 20.8%

Pre–post study design withno long-term follow up

Excluded non-diabetic KTRsSingle centre study

No reporting of BMI at 6months

Schmid-Mohler et al. [43](Switzerland) 12

n = 123 KTR andKidney-pancreas Tx

(120 KTR)

IG:Control + 8-month

nurse-led interventionincluding dietary and PA

counselling withmotivational interviewing

and action planningCG:

A single nurse-lededucation session with

booklet

Primary:Difference in BMI (baseline

to 8 months) in patients

with a BMI of ≥18.5 kg/m2

Secondary:change in BMI baseline to 12

months, Rx adherence,satisfaction withcounselling, BC

(bioimpedance), PA (IPAQ),patient assessment of

chronic illness care PACIC)

Primary:No significant

between-group difference inchange in BMI or BC from

baseline to 8 months, orBaseline to 12 months

Secondary:No significant differences

between-group in BC, stepsor IPAQ

IG more chronic care relatedactivities (PACIC)

High acceptability IG88.5% IG received ≥7

sessionsSignificant difference in

PACIC in all but one scoreIG vs. CG

No difference betweengroups in satisfaction with

counselling

AEs not reportedSample includes

kidney-pancreas TxMeans and SD for KTR (n =

120) provided on request.There was no significantbetween-group in BW orBMI at any timepoint in

KTRs

Serper et al. [44](USA) 4

n = 127 KTR and LiverTransplants (65 KTR).

Participants needed to owna smartphone compatible

with wearable accelerometer

IG1:Device only group, access toonline portal with education

materials and questions +control education

IG2:Control education +

Intervention 1 + 2 plusbi-weekly texts, step goals

and financial incentivesCG:

standard education onhealthy diet, food hygiene

and PA

Primary:Change in BW from baseline

to 4 monthsSecondary:

Daily steps—proportion ofpatients achieving > 7000

steps/day, and continuousdaily step data

Primary:No significant difference in

weight gain between allthree groups (IG1, IG2 and

CG)Secondary:

Significantly higher stepcount reported in IG2 vs.

IG1 (p < 0.001)Retention rate 92.1%

Adherence final studyweight assessment 88%

74% IG2 adhered to theirstep targets

Study increased motivationto monitor weight and

increase PASome participantsdisappointed with

randomisationSome IG patients requested

ability to track differentactivities, and have non-step

related goals

No AEs associated withstudy

Combined sample (KTR andLiver Transplant)

Unique approach withfinancial incentives

Diet education not designedfor weight management

No longer-term follow-upBMI not reported

Kidney Dial. 2021, 1 107

Table 2. Cont.

First Author, Year (Countryof Origin)

StudyDuration (Months) Sample Groups Outcomes (Primary and

Secondary)Results (for Primary and

Secondary Outcomes) Comments

Gibson et al. [53](USA) 6

n = 10 KTR, 6–12 monthspost-transplant,

Mean age 44 years,

BMI >22 kg/m2,

IG: 6-month combined Rxvia telehealth (dietitian-led,

12 weeks of one-hourweekly calls and PA classes).

Followed by 12 weeks ofmaintenance. Provided withtablet to track food and vegintake, whole grains intake,water intake, steps, and PA

weeklyCG: Standardised educationto follow healthy eating and

PA. Provided with tabletand tracking (as above). Did

not receive weekly videocalls or PA classes

Primary:Primary outcomes relate to

feasibility (recruitment,adherence, attendance)

Secondary:Provide estimates of Rxeffectiveness including

changes to PA, food intake(fruit, veg, whole-grain, andwater). Secondary outcomes

included weight gain(baseline to six months), BW,BMI, BP, PA (accelerometer),QoL, Dietary intake (3-day

food diary), qualitativeinterviews for strengths and

weakness of intervention

Primary:78% attendance telehealth

sessions (IG)86% adherence to weekly

behaviour tracking viatablet

All patients attended week12 study assessments

Tracking increasedawareness but some had

problemsAll would recommend trial

to othersTailored education and the

ability to complete Rx athome was valued

Secondary:Weight gain and BMI

greater in IG versus CHGQoL improvements greater

in CG versus IGNo difference in BP and PA

between groupsImproved diet quality in

both groups

Specific recruitment criteriaincluded the ability to take

part in six-month trial,ability to report data weekly

(by phone, fax, email),access to the internet,

English speaking,willingness to be

randomisedOne participant withdrewdue to time commitments

Note. KTRs = kidney transplant recipient, IG = intervention Group, CG = control group, BW = body weight (kg), BMI = body mass index(kg/m2), HDL = high-density lipoprotein, LDL = low-density lipoprotein, Tx = transplant, AE = adverse event, AT = aerobic exercisetraining, Vo2 peak = peak oxygen update, FM = fat mass, LTM = lean tissue mass, BC = body composition, DEXA = dual-energy X-rayabsorptiometry, QoL = quality of life, SF-36 = short form 36, PA = physical activity, PWV = pulse wave velocity, CiMT = carotid intima-media thickness via ultrasound, ITT = intention to treat analysis, KTx = kidney transplant, RT = resistance training, OGTT = oral glucosetolerance test, BP = blood pressure, ET = exercise training, ANCOVA = analysis of covariance analysis, STS = sit to stand test, NZPA = NewZealand physical activity questionnaire, HbA1c = haemoglobin A1c, PTDM = post-transplant diabetes mellitus, GPPAQ = General PracticePhysical Activity Questionnaire, DASI = Dukes Activity Status Index, EQ-5D = EuroQoL five dimension scale, BAME = black, Asian andminority ethnicity, IPAQ = international physical activity questionnaire, PACIC = patient assessment of chronic illness care questionnaire,SD = standard deviation, Rx = Intervention.

3.2. Characteristics of Interventions

Methodological variation was evident across the ten RCTs included in this systematicreview and meta-analysis. One study included a 12-month diet only intervention [45],three studies [36,39,46] included exercise only interventions ranging from three to twelvemonths, and six RCTs included combined interventions [43,44,48,49,53,54]. The RCTs withcombined interventions varied significantly in duration between fourteen weeks [44], sixmonths [48,53], eight months [43], and one year [49,54]. Two studies [48,54] did not reportthe specifics of the PA component of the combined intervention.

Two RCTs [39,44] included three treatment arms. O’Connor et al. [39] compared threemonths of either aerobic training or resistance training to usual care. Serper et al. [44]randomised kidney and liver transplant recipients into the following three groups: (1) ed-ucation, (2) access to an online platform and a step tracking device, and (3) access to theonline platform and step tracking device, plus text message support, automated step goals,and financial incentives [44]. However, limited information was provided on the educationcontent within the treatment website.

The healthcare professionals providing interventions was variable. Some were dietitian-led face-to-face visits or telephone calls [45,48,54], one was provided by a physiothera-pist [39], two were provided by exercise professionals [46,49], and one RCT did not specifythe intervention provider [36]. Two recent RCTs [43,53] included combined interventionswith a digital delivery component. Serper et al. [44], provided both the two interventiongroups with access to a combined online platform. Gibson et al. [53] provided both groupswith a tablet to track healthy behaviours weekly. The intervention group were providedwith dietary and PA interventions delivered by video teleconference calls [53].

Whilst some interventions describe common strategies to promote behaviour-changesuch as goal setting [43,48,53,54] and motivational interviewing techniques [43,54], onlythree trials [43,48,54] explicitly described BCTs in reference to the BCT taxonomy [55].Self-monitoring, ‘SMART goals’ [56], action planning, social support, and revision of goalswere the most common BCTs. Table 3 summarises the interventions of the RCTs. See TableS6 for tabulated descriptions of the interventions for the non-RCTs.

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Table 3. Detailed description of interventions RCTs (n = 10).

Study Rx type Rx Description Rx BehaviourComponents Provider Duration

(Months) Frequency Intensity Type of ET Time(Minutes)

Lawrenceet al.[45]

Diet

Written andverbal edu to

reducehyperlipidaemiaDiet: 30% totalenergy from fatand 50% fromcarbohydrates

Mode: NI,assume F2F

NI RD 12 s NI NA NA NA

Painteret al.[36]

Exercise

Home ET(independent)

Fortnightlyphone calls

Mode: Telephone

Self-monitoringbehaviour(diaries)

Phone calls forencouragement

NI 12 4x week

60–65%HRM,↑ 75–80%

HRM

AT ≥30

Tzvetanovet al.[49]

Combined

Combination of1:1 ET + CBT +

nutritionTopics includereduce sodium,

emotional eating,increase protein,

reducecholesterol, andbalanced meals

Aims of Rx; buildmuscle tissue,

change thoughts,and

empowermentMode: F2F

CBT details notprovided P.Tr 12 ET 2x week Not

specified RT 60

Kareliset al.[46]

Exercise

ET programme of7 exercises

Upper and lowerlimb RT

Mode: F2Fsupervised

NI Kinesiologystudent

16 weeks(≈3.68

months)

3x week (1xweek

supervised)80% 1RM RT 45–60

O’Connoret al.[39]

Exercise

2 interventiongroups; AT andRT compared

with UCMode: F2F

Motivationalinterviewing PT 3

3x week(2x

supervisedgroup,1x not

supervised)

AT: 80%HRR

RT: 80%1RM

1–2 sets 10reps, ↑ to 3

sets

AT or RT vs.UC

60 AT or RT30

min/weekedu (AT and

RT)

Henggeleret al.[54]

Combined

Multi-professional and

components12 sessions (4x

UC sessions, plus8 additional

nutritionsessions) with

RDExercise and PA

componentMode: NI,

assume F2F

SMART goalsetting and

revision of goalsMotivationalinterviewing

Action planningSelf-monitoring

RDEx.Phys:

ET and PA12

12x RDfollow-ups3x ET with

Ex.Phys

‘Tailored PAadvice’,

No furtherdetail

NI NI PA

Kidney Dial. 2021, 1 109

Table 3. Cont.

Study Rx type Rx Description Rx BehaviourComponents Provider Duration

(Months) Frequency Intensity Type of ET Time(Minutes)

Kuningaset al.[48]

Combined

Combinedlifestyle Rx to

prevent PTDM,Dietary habits,Personalised

healthy eating,edu based on

Diabetes UK andPublic Health

England,Graded ET,

Exercise diary,Mode: F2F and

phone follow-up

BCTs used:Information onconsequences,feedback on

personalinformationpromptingintention

formation,SMART goals,graded tasks,

self-monitoring,revision of goals,

social support

RD 6

4x F2F 1:1with RD

RD phoneconsultantbetweeneach F2Fsession

Specifics notReported AT NI

Schmid-Mohler

et al.[43]

Combined

Developedbrochure edu

food types andhygiene, and

encouraging PAInitial 1:1 edusession with

brochure as perUC group +8

APN-led sessionsMode: F2F or

phone

BCTs used:goal setting,

problem solving,action planning,

review behaviourand outcome

goals,feedback onbehaviour,

self-monitoringof behaviour,instruction on

how to performbehaviour,

informationabout health

consequences,prompts/cues,habit formation

and reversal,focus on past

success,self-monitoring

of behavioursocial support

APN(trained in

motiva-tional

interview-ing)

8

Combinationof F2F and

phonefollow-up

9 sessions intotal.

Specifics PAnot reported NI 35

Serperet al.[44]

Combined +online

IG1: Device only:Step-counting

device,Website withresources on

healthy eatingand PA,Health

knowledgequestionnairesMode: online

IG2. Device andRx:

As above+ Financialincentives,

+ Automated stepgoals,

+ Bi-weekly textmessages, for

healthquestionnaire

Mode: online andtext

prompts/cues(text),

financialincentives(rewards)

1. Website2. websiteand text

messages(auto-

mated) byresearch

team

14 weeks(≈3.22

months)

1. Onlinewebsite,

step-recording

device2. onlinewebsite,

step-recording

device andtext support

1. Deviceonly—no

prescription2. Deviceand Rx:baseline

stepsincreased

15% every 2weeks until

reached 7000steps/day

AT- steps NI

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Table 3. Cont.

Study Rx type Rx Description Rx BehaviourComponents Provider Duration

(Months) Frequency Intensity Type of ET Time(Minutes)

Gibsonet al.[53]

Combined+tracking

+video calls

both groupsgiven tablets forweekly tracking

(fruit/veg,wholegrains,

water, steps, andPA)

IG: 6-monthsvideo calls:Tracking,

12 weeks of dietEdu (DASH diet),12 weeks group

PA,12 weeks

maintenanceusing tracking

onlyMode: video calls

Rx informed bythe Social

Cognitive Theory[57] and

self-efficacy [58]Self-monitoring

Goal setting

Tracking(not super-vised) on

tabletDiet Edu

(RD),group PA(exerciseprofes-sional)

6 Weekly

Moderateintensity

(3–6metabolicequivalent

of task)

NI

Diet 1:1 andgroup PA 30min/week

(total 60min/week)Encouragedto do 10–15

min PA/day

Note. Rx indicates treatment, ET = exercise training, Edu = education, F2F = face-to-face, NI = no information, RD = renal dieti-tian, NA = not applicable, KTx = Kidney transplant, PT = Physiotherapist, Ax = assessment, AT = aerobic training, HR = hear rate,RT = resistance training, BCTs = behaviour change techniques, HRM = heart rate max, Phys. = Physician, 1:1 = one on one (individ-ual treatment), CBT = cognitive behavioural therapy, P.Tr = Personal trainer, PA = physical activity, 1RM = one repetition maximum,UC = usual care, HRR= heart rate reserve, reps = repetitions, SMART goals = specific measurable achievable realistic and timed goals,Ex. Phys = Exercise Physiologist, PTDM = post-transplant diabetes mellitus, APN = advanced practice nurse, IG = intervention group,DASH = dietary approaches to stop hypertension diet.

4. Risk-of-Bias

Minor disagreements between the two reviewers (E.M.C. and E.Mc.) on quality assess-ments were resolved through discussion, with no need to involve a third reviewer. FourRCTs were classified as ‘low-risk’ [43,48,53,54], one was classified as ‘some concerns’ [44]for risk of bias, and five were classified as ‘high-risk’ overall [36,39,45,46,49]. The ‘High-risk’assessment was predominantly due to inadequate reporting on deviation from protocoland missing data. There was a wide variation in the risk-of-bias for the non-RCTs (Supple-mentary Material, Figure S1). Figure 2 demonstrates the risk-of-bias plots created using therisk-of-bias visualisation tool [59].

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Figure 2. Risk−of−bias plot for RCTs (n = 10).

3.4. Body Weight and BMI Nine [36,39,43–46,49,53,54] of the ten RCTs reported no effect of interventions on

body weight or BMI values. However, Kuningas et al. [48] reported a change to these measures as a secondary outcome. A total of 130 non-diabetic KTRs were randomised to either a passive education booklet or a dietitian-led six-month intervention involving di-etary education, PA plans, and BCTs [48] (Figure 3). Whilst the study revealed no signifi-cant difference in its primary outcome of glucose metabolism, the authors report a signif-icant difference in the change in body weight over the 6-month study of −2.47 kg (95% CI 0.401 to −0.92, p = 0.002) [48]. BMI post-intervention values were not presented by the au-thors. However, there was a significant mean difference in fat mass favouring the inter-vention group participants [48]. The risk-of-bias was categorised as ‘low’.

Figure 3. Meta-analysis body weight (post-intervention values). Note. Post-intervention values used for meta-analysis. Scheme 45. and Henggeler et al. [54]. Schmid-Mohler et al. [43] provided BW and BMI data for KTR alone (n = 120) on request. Studies with multiple intervention arms [39,44] were combined. Fractions in the study column depict the length of interventions in months (/12) or weeks (/52), ET refers to exercise intervention and Rx = intervention.

3.5. Meta-Analyses Body Weight and BMI Eight out of the ten final RCTs [36,39,43,44,46,48,53,54] reported post-intervention

body weight values. Eight reported post-intervention BMI values [36,38,43,45,46,49,53,54] and were included in the meta-analysis. Despite variation in the methods and participant characteristics between the included RCTs, the measures of statistical heterogeneity were

Figure 2. Risk−of−bias plot for RCTs (n = 10).

5. Body Weight and BMI

Nine [36,39,43–46,49,53,54] of the ten RCTs reported no effect of interventions on bodyweight or BMI values. However, Kuningas et al. [48] reported a change to these measures

Kidney Dial. 2021, 1 111

as a secondary outcome. A total of 130 non-diabetic KTRs were randomised to eithera passive education booklet or a dietitian-led six-month intervention involving dietaryeducation, PA plans, and BCTs [48] (Figure 3). Whilst the study revealed no significantdifference in its primary outcome of glucose metabolism, the authors report a significantdifference in the change in body weight over the 6-month study of −2.47 kg (95% CI 0.401to −0.92, p = 0.002) [48]. BMI post-intervention values were not presented by the authors.However, there was a significant mean difference in fat mass favouring the interventiongroup participants [48]. The risk-of-bias was categorised as ‘low’.

Kidney Dial. 2021, 1, 12

Figure 2. Risk−of−bias plot for RCTs (n = 10).

3.4. Body Weight and BMI Nine [36,39,43–46,49,53,54] of the ten RCTs reported no effect of interventions on

body weight or BMI values. However, Kuningas et al. [48] reported a change to these measures as a secondary outcome. A total of 130 non-diabetic KTRs were randomised to either a passive education booklet or a dietitian-led six-month intervention involving di-etary education, PA plans, and BCTs [48] (Figure 3). Whilst the study revealed no signifi-cant difference in its primary outcome of glucose metabolism, the authors report a signif-icant difference in the change in body weight over the 6-month study of −2.47 kg (95% CI 0.401 to −0.92, p = 0.002) [48]. BMI post-intervention values were not presented by the au-thors. However, there was a significant mean difference in fat mass favouring the inter-vention group participants [48]. The risk-of-bias was categorised as ‘low’.

Figure 3. Meta-analysis body weight (post-intervention values). Note. Post-intervention values used for meta-analysis. Scheme 45. and Henggeler et al. [54]. Schmid-Mohler et al. [43] provided BW and BMI data for KTR alone (n = 120) on request. Studies with multiple intervention arms [39,44] were combined. Fractions in the study column depict the length of interventions in months (/12) or weeks (/52), ET refers to exercise intervention and Rx = intervention.

3.5. Meta-Analyses Body Weight and BMI Eight out of the ten final RCTs [36,39,43,44,46,48,53,54] reported post-intervention

body weight values. Eight reported post-intervention BMI values [36,38,43,45,46,49,53,54] and were included in the meta-analysis. Despite variation in the methods and participant characteristics between the included RCTs, the measures of statistical heterogeneity were

Figure 3. Meta-analysis body weight (post-intervention values). Note. Post-intervention values used for meta-analysis.Scheme 45. and Henggeler et al. [54]. Schmid-Mohler et al. [43] provided BW and BMI data for KTR alone (n = 120) onrequest. Studies with multiple intervention arms [39,44] were combined. Fractions in the study column depict the length ofinterventions in months (/12) or weeks (/52), ET refers to exercise intervention and Rx = intervention.

6. Meta-Analyses Body Weight and BMI

Eight out of the ten final RCTs [36,39,43,44,46,48,53,54] reported post-interventionbody weight values. Eight reported post-intervention BMI values [36,38,43,45,46,49,53,54]and were included in the meta-analysis. Despite variation in the methods and participantcharacteristics between the included RCTs, the measures of statistical heterogeneity werenot significant for BW (Chi2 7, n = 575, p = 0.6, I2 = 0%) or BMI (Chi2 7, n = 383, p = 0.43,I2 = 0%). The pooled data from 575 KTRs (Figure 3) revealed a non-significant meandifference in body weight (effect size, −2.50 kg, 95% confidence interval (95% CI) −5.22 to0.22). The pooled data from 383 KTRs revealed a non-significant mean difference in BMI(−0.4 kg/m2, 95% CI –1.33 to 0.53). See Figure 4.

Kidney Dial. 2021, 1, 13

not significant for BW (Chi2 7, n = 575, p = 0.6, I2 = 0%) or BMI (Chi2 7, n = 383, p = 0.43, I2 = 0%). The pooled data from 575 KTRs (Figure 3) revealed a non-significant mean differ-ence in body weight (effect size, −2.50 kg, 95% confidence interval (95% CI) −5.22 to 0.22). The pooled data from 383 KTRs revealed a non-significant mean difference in BMI (−0.4 kg/m2, 95% CI –1.33 to 0.53). See Figure 4.

Figure 4. Meta-analysis BMI (post-intervention values). Note. Post-intervention values used for meta-analysis. BMI was not reported in O’Connor et al. [39]. Therefore, * indicates BMI from pri-mary study manuscript [38]. BMI values from Tzvetanov et al. [49] were calculated from mean change and baseline values. Standard deviations were calculated from SEM in Henggeler et al. [54]. Fractions in the study column depict the length of interventions in months (/12) or weeks (/52), ET refers to exercise intervention and Rx = intervention.

Exploratory post hoc sensitivity analysis was performed on pooling the effects of the combined interventions and the single modality interventions (exercise or diet alone) to further explore the body weight and BMI values. Sensitivity analysis (Supplementary ma-terial, Table S7) revealed that combined interventions [43,44,48,53,54] could have the po-tential to influence post-intervention body weight values. These findings were not echoed in the sensitivity analysis for the post-intervention BMI values. Funnel plots were com-pleted to assess publication bias (Figure 5A,B). These demonstrated the potential for pub-lication bias.

(A)

Figure 4. Meta-analysis BMI (post-intervention values). Note. Post-intervention values used for meta-analysis. BMI wasnot reported in O’Connor et al. [39]. Therefore, * indicates BMI from primary study manuscript [38]. BMI values fromTzvetanov et al. [49] were calculated from mean change and baseline values. Standard deviations were calculated fromSEM in Henggeler et al. [54]. Fractions in the study column depict the length of interventions in months (/12) or weeks(/52), ET refers to exercise intervention and Rx = intervention.

Kidney Dial. 2021, 1 112

Exploratory post hoc sensitivity analysis was performed on pooling the effects ofthe combined interventions and the single modality interventions (exercise or diet alone)to further explore the body weight and BMI values. Sensitivity analysis (SupplementaryMaterial, Table S7) revealed that combined interventions [43,44,48,53,54] could have thepotential to influence post-intervention body weight values. These findings were notechoed in the sensitivity analysis for the post-intervention BMI values. Funnel plots werecompleted to assess publication bias (Figure 5A,B). These demonstrated the potential forpublication bias.

Kidney Dial. 2021, 1, 13

not significant for BW (Chi2 7, n = 575, p = 0.6, I2 = 0%) or BMI (Chi2 7, n = 383, p = 0.43, I2 = 0%). The pooled data from 575 KTRs (Figure 3) revealed a non-significant mean differ-ence in body weight (effect size, −2.50 kg, 95% confidence interval (95% CI) −5.22 to 0.22). The pooled data from 383 KTRs revealed a non-significant mean difference in BMI (−0.4 kg/m2, 95% CI –1.33 to 0.53). See Figure 4.

Figure 4. Meta-analysis BMI (post-intervention values). Note. Post-intervention values used for meta-analysis. BMI was not reported in O’Connor et al. [39]. Therefore, * indicates BMI from pri-mary study manuscript [38]. BMI values from Tzvetanov et al. [49] were calculated from mean change and baseline values. Standard deviations were calculated from SEM in Henggeler et al. [54]. Fractions in the study column depict the length of interventions in months (/12) or weeks (/52), ET refers to exercise intervention and Rx = intervention.

Exploratory post hoc sensitivity analysis was performed on pooling the effects of the combined interventions and the single modality interventions (exercise or diet alone) to further explore the body weight and BMI values. Sensitivity analysis (Supplementary ma-terial, Table S7) revealed that combined interventions [43,44,48,53,54] could have the po-tential to influence post-intervention body weight values. These findings were not echoed in the sensitivity analysis for the post-intervention BMI values. Funnel plots were com-pleted to assess publication bias (Figure 5A,B). These demonstrated the potential for pub-lication bias.

(A)

Kidney Dial. 2021, 1, 14

(B)

Figure 5. Funnel plots to assess publication bias. (A). Funnel plot for post−intervention body weight (kg). (B). Funnel plot for post−intervention BMI(kg/m2). Note. Where SE = standard error, MD = mean difference

3.6. Secondary Outcomes Meta-analyses were not performed on secondary outcomes due to the large variation

of measurement tools utilised (refer to Tables 2 and 3), and the limited number of RCTs. Five RCTs assessed body composition [36,43,46,48,54]. No studies reported a significant difference in lean tissue mass. Kuningas et al. [48] reported a significant mean difference in fat mass favouring the treatment group in their dietitian-led combined intervention (mean difference −1.54 kg (−2.95 to −0.13), p = 0.033). Another study [49] reported a mar-ginal decrease in the percentage fat mass; however, this outcome was only captured in the treatment group due to significant loss to follow-up. Four studies reported an increase in fat mass in all the participants [36,41,46,54].

Four studies measured physical function [48,49,51,54] using different measures. One study reported a significant difference in physical function; however, data were only available for the intervention group [49].

Three studies used different questionnaires to measure PA [43,48,54]. One study [52] reported an increase in the PA of the treatment group but provided no further infor-mation. Another study [47] reported a significant increase in the percentage of partici-pants achieving two hours or more of PA per-week (28% vs. 71%, p < 0.001); however the data are not presented for the comparator group. One study [36] reported a higher pro-portion of self-reported PA levels at twelve months in the treatment group versus the usual care group (67% vs. 36%, p = 0.02). Three studies reported no significant between-group difference in PA [43,48,53]. One RCT demonstrated a high step count of over ten thousand steps-per-day in both groups [43]. Serper et al. [44] reported the group receiving the step tracker, website, and online-intervention had a higher step count than the group receiving the device alone (p < 0.001).

No studies assessed self-efficacy. One study [48] reported no between-group differ-ence in the questionnaires assessing situational motivation scores and depression symp-toms. Another study [49] reported motivation via the index of personality styles question-naire in the intervention group only.

Figure 5. Funnel plots to assess publication bias. (A). Funnel plot for post−intervention bodyweight (kg). (B). Funnel plot for post−intervention BMI(kg/m2). Note. Where SE = standard error,MD = mean difference.

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7. Secondary Outcomes

Meta-analyses were not performed on secondary outcomes due to the large variationof measurement tools utilised (refer to Tables 2 and 3), and the limited number of RCTs.Five RCTs assessed body composition [36,43,46,48,54]. No studies reported a significantdifference in lean tissue mass. Kuningas et al. [48] reported a significant mean differencein fat mass favouring the treatment group in their dietitian-led combined intervention(mean difference −1.54 kg (−2.95 to −0.13), p = 0.033). Another study [49] reported amarginal decrease in the percentage fat mass; however, this outcome was only captured inthe treatment group due to significant loss to follow-up. Four studies reported an increasein fat mass in all the participants [36,41,46,54].

Four studies measured physical function [48,49,51,54] using different measures. Onestudy reported a significant difference in physical function; however, data were onlyavailable for the intervention group [49].

Three studies used different questionnaires to measure PA [43,48,54]. One study [52]reported an increase in the PA of the treatment group but provided no further informa-tion. Another study [47] reported a significant increase in the percentage of participantsachieving two hours or more of PA per-week (28% vs. 71%, p < 0.001); however the data arenot presented for the comparator group. One study [36] reported a higher proportion ofself-reported PA levels at twelve months in the treatment group versus the usual care group(67% vs. 36%, p = 0.02). Three studies reported no significant between-group difference inPA [43,48,53]. One RCT demonstrated a high step count of over ten thousand steps-per-dayin both groups [43]. Serper et al. [44] reported the group receiving the step tracker, website,and online-intervention had a higher step count than the group receiving the device alone(p < 0.001).

No studies assessed self-efficacy. One study [48] reported no between-group differencein the questionnaires assessing situational motivation scores and depression symptoms.Another study [49] reported motivation via the index of personality styles questionnaire inthe intervention group only.

8. Discussion8.1. Summary of Main Findings

The current evidence evaluating interventions to address post-transplant weight gainare limited, with only ten RCTs. These studies had mainly small samples, limited power,a lack of long-term follow-up, variable sample characteristics, and variable interventiontypes and duration. This limits the ability to perform pooled estimates. The meta-analysesof post-intervention body weight and BMI values revealed no significant effect on bodyweight or BMI. Whilst the meta-analysis revealed no significant statistical heterogeneity,there was methodological heterogeneity across the included RCTs. When performingexploratory post hoc sensitivity analysis, the combined interventions revealed the potentialto influence body weight, but not BMI in new KTRs.

A study by Kuningas et al. [48] was the only RCT to show a significant differencein body weight following a six-month complex intervention involving dietetic education,physical activity plans, and BCTs. The authors reported a significant mean differencein change in weight of −2.47 kg at six months, and a significant mean difference in fatmass favouring the treatment group. Whilst this study was powered for insulin sensitivity,the relatively large sample of 130 participants and it’s ‘low risk’ of bias provides someconfidence in its findings. Whilst the study excluded diabetic KTRs and did not includea long-term follow-up, it provides a promising basis of intervention design for futureresearch in this field.

The study design could have impacted the ability for RCTs using combined interven-tions [43,44,49,53,54] to effect post-intervention body weight and BMI values. The lackof between-group treatment effect in Henggeler et al. [54] could have been influenced bythe higher standard of usual care, and the exercise component may not have been of asufficient dose to elicit change. Schmid-Mohler et al. [43] acknowledged that irrespective

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of the treatment groups, both groups had high levels of PA, which could have influencedtheir results.

Tzvetanov et al. [49] reported no significant between-group difference in BMI betweenthe 12-month combined intervention group and the control group. Change in body weightwas not reported. This study was assessed to have ‘high-risk’ with the risk of bias due toits small sample size (n = 12) and large number of dropouts, particularly in the controlgroup, impacting data collection on important outcomes such as body composition.

Serper et al. [44] reported no significant between-group difference in the change inbody weight from baseline to four months. The authors acknowledged that the dietarycomponent of the online intervention was not designed for weight management, theintervention was relatively short in duration (14 weeks), and there was no long-termfollow-up [44]. In addition, there was the potential of contamination bias, with some ofthe control group participants purchasing wearable step trackers or using smart phoneapplications in response to randomisation [44]. The participants randomised into the steptracker device with the text message and financial incentives displayed a greater numberof steps than those in the step tracking device group, suggesting a potential benefit ofthe text reminders and financial incentives on PA behaviour. This study was assessed as‘some-concerns’ for risk of bias. However, KTR data are not presented in isolation of thecombined transplant sample, making it difficult to determine the effects of the interventionon KTRs alone.

Gibson et al. [53] reported that the intervention group, who received six months ofcombined intervention with video teleconference calls, increased their body weight andBMI in comparison to the usual care group. Measures of body composition were notincluded in this trial. This feasibility RCT had a small sample (n = 10). It does, however,provide evidence of strong adherence rates in the intervention group and qualitativefindings to support further investigation into online interventions to support new KTRs.

Previous systematic reviews of exercise interventions in KTRs have shown favourableeffects on exercise clinical outcomes but no consistent change in body weight [15,17].Therefore, it is unsurprising that our systematic review confirmed that exercise or PAinterventions alone [36,39,46] did not show favourable effects on body weight or BMI. Thisis likely due to the trial and intervention design, with exercise specific outcomes beingselected to align with exercise intervention targets [60], rather than targeting behaviourchange. It is also unsurprising that the one RCT [45] included in this systematic reviewthat compared 12 months of dietary intervention with usual care did not show a significantimpact in BMI [45]. Combined interventions are likely to be needed to address the complexclinical problem of acute post-transplant weight gain.

A recent Cochrane review by Conley et al. [61] reviewed interventions for weightloss in obese and overweight participants living with chronic kidney disease (includingKTRs). The authors [61] reported no difference in total weight loss when comparing weightloss interventions (dietary, physical activity, behavioural, or combined) to usual care inKTRs. However, this systematic review focused on people who were already classifiedas overweight and obese, investigated weight loss rather than weight gain prevention,and included participants with older transplants, making it difficult to infer the effects onweight gain in the acute post-transplant period.

8.2. Implications for Clinical Practice

Fear of harming the new kidney transplant has been reported by KTRs [11,62,63].KTRs have reported receiving limited education from clinicians regarding the type anddose of recommended exercise after kidney transplant [62]. KTRs have expressed theneed for early interventions that support PA behaviour-change [14] and a healthy lifestylepost-transplantation [11]. Routine access to both physiotherapists and dietitians is notavailable for KTRs in the UK. A recent survey of the UK transplant units conducted byKostakis et al. [4] revealed that despite clinicians agreeing that obesity and a high BMInegatively affects transplant outcomes, there was limited clinical support for weight control

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for new KTRs. Thus, data regarding the effect of interventions to prevent weight gain innew KTRs are limited and are urgently needed to inform clinical practice.

8.3. Implications for Future Research

This systematic review and meta-analysis suggest that there is insufficient evidenceto advise clinical practice in this field, and that more research is warranted. Sufficientlypowered RCTs, with clear reporting of complex multi-component interventions usingrecognised checklists such as the CReDECI criteria [64], the TiDieR checklist [65], andreference to the BCT taxonomies [55] are required. It would be of particular interest forfuture studies to include combined interventions, with recognised BCTs, similar to thosedisplayed in Kuningas et al. [48], to address both physical activity and healthy eatingbehaviours. In addition, only one RCT in this review [39] reported a twelve-month follow-up after a period of intervention cessation. There is, therefore, a need for RCTs to investigatelonger-term outcomes.

There was significant variation in the methods utilised to assess body composition,physical function, and physical activity in new KTRs, precluding the ability to perform ameta-analysis for these secondary outcomes. Whilst weight gain is a clinically importantissue for new KTRs, future studies would benefit from including the patient-centredoutcomes, such as ‘life participation’, that have been listed as a core outcome measure by agroup of international KTRs and healthcare professionals from the Standardized Outcomesin Nephrology (SONG) Transplantation group [66].

Given there is no recognised intervention to prevent weight gain in new KTRs, anexploration of other modes of delivery, such as online interventions, would benefit fromfurther research. Only two studies [44,53] identified in this systematic review included anelement of digital delivery to the intervention group. Despite both RCTs not revealing sig-nificant differences in body weight or BMI, they did demonstrate improved PA levels [44],acceptability, and good adherence rates to the online interventions [44,53].

A recent Cochrane systematic review [67] evaluated the risks and benefits of onlinee-health interventions for people living with kidney disease (including KTRs). The re-view [67] concluded that there is low quality evidence for e-health interventions, andfurther research with interventions that utilise theoretical frameworks, self-monitoringand personalised education are warranted. Given the recent need for virtual clinics tosupport transplant patients during the COVID-19 pandemic [68], research exploring theuse of online delivery of interventions to support KTRs requires further investigation.

8.4. Strengths and Limitations

To our knowledge, this is the first systematic review and meta-analysis that includedexercise, PA, dietary, or combined interventions and their effect on body weight in newKTRs. Previous reviews have focused on either exercise or PA alone, [15–17] or excludedcombined interventions [18]. There is a need for further research on dietary managementfor KTRs [18,69,70]. This systematic review focused on body weight and BMI as primaryoutcomes. Therefore, it is possible that further studies reporting secondary outcomes, butnot body weight or BMI, were excluded in this search.

This systematic review focused on KTRs rather than all SOTs. However, KTRs haverequested specific education and support [11,71], experience a unique fear avoidancepattern associated with PA [63], and experience rapid weight gain in the acute post-operative period [3]. Furthermore, this review focused on KTRs within the first year oftransplant surgery. Studies that include participants with an older transplant vintage wereexcluded, which may have precluded additional insight into this research area. However,as weight gain within the first year is associated with adverse clinical outcomes [6,72], theauthors felt it was important to investigate the first year post kidney transplantation.

The authors acknowledge the impact that the methodological variation between thefinal RCTs (sample characteristics, intervention type, dose, and duration) may have hadon the validity of the pooled effects of interventions on body weight or BMI. Statistical

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heterogeneity was not significant. By performing the meta-analyses on body weight andBMI, and exploring this with sensitivity analysis, this systematic review provides novelimplications for future research studies in this field.

9. Conclusions

This is the first systematic review and meta-analysis to examine the evidence on eitherdietetic, exercise, or combined interventions on body weight and BMI within the first yearof receiving a kidney transplant. There is limited evidence in the field, and we encouragefurther adequately powered theoretically informed RCTs, with pragmatic inclusion criteria,clear reporting of intervention components, and long-term follow-up, to further answerthis important clinical question of acute weight gain post kidney transplantation.

Supplementary Materials: The following are available online at https://www.mdpi.com/article/10.3390/kidneydial1020014/s1, Figure S1: Risk-of-bias plots for Non-RCTs (n = 6), Table S1: PRISMAchecklist, Table S2: Search strategy, Table S3: Screening form, Table S4: Detailed sample characteristics,Table S5: Study characteristics of non-RCTs, Table S6: Details of intervention non-RCTs (n = 6),Table S7: Sensitivity analysis.

Author Contributions: The search was conducted by E.M.C. and J.G. who collected the data. Qualityassessments were independently conducted by E.M.C. and E.M. on individual papers. All authors(E.M.C., E.M., J.G., K.B., J.C. and S.A.G.) contributed to the writing of the manuscript and the searchprotocol. All authors have read and agreed to the published version of the manuscript.

Funding: The work is supported by Ellen Castle’s PhD Grant by Kidney Research UK (AHPF_001_20171122).Sharlene Greenwood is supported by the NIHR Advanced Research Fellowship (ICA-CL-2017-03-020).Emily McBride was funded by the National Institute for Health Research (NIHR) (DRF-2017-10-105);the views expressed in this paper are not necessarily those of the NHS, the NIHR, Kidney ResearchUK, or the Department of Health and Social Care.

Institutional Review Board Statement: Not applicable.

Informed Consent Statement: Not applicable.

Data Availability Statement: Data is contained within the article or Supplementary Material. Thedata presented in this study are available in this article and included Supplementary Material.

Acknowledgments: The authors acknowledge Leorita Joseph Henry, Clinical Support Librarian,King’s College Hospital London (for her invaluable professional advice and support in developing thesearch strategy). The authors acknowledge Karen Poole and John Woodcock, Library and Collections,King’s College London (for their professional assistance via the Advanced Searching for systematicreviews discussion forum for their feedback on refining the search strategy).

Conflicts of Interest: The authors declare no conflict of interest. The funders had no role in the designof the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, orin the decision to publish the results.

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